The invention relates to derivatives of dextran endowed, particularly with anti-coagulant properties and anti-complementary properties, to their preparation and to their biological uses.
It is known that heparin is widely used as an antithrombotic medicament by reason of its high anti-coagulant properties.
Recent work has also shown its action with respect to the inactivation of the complementary system, that is to say the group of plasma proteins playing an essential role in the immunitary defence of the organism.
The heterogeneity of its chains, particularly, as regards their composition and their length, renders however difficult study of the structures responsible for its properties.
Numerous researches have been undertaken to develop products having at least certain of the specific properties of heparin, but of well-defined structure thus capable of serving as a model for the study of the corresponding mechanisms brought into play.
Some of the co-inventors of the invention have prepared and disclosed (FR Pat. No. 2 461 724 and EP patent application No. 80 401053.6) compounds having anti-coagulant properties, consisting of polymers having the following groups: EQU --SO.sub.3 R.sub.1, --R.sub.3 SO.sub.3 R.sub.1, --SO.sub.2 R.sub.2, --R.sub.3 --SO.sub.2 --R.sub.2 and --CH.sub.2 --CO--NH--CHR--COOH--
wherein
R.sub.1 is an hydrogen atom or a physiologically acceptable metal PA1 R.sub.2 is an aminoacid residue bound to --SO.sub.2 -- through an amino function PA1 R.sub.3 is a --CH.sub.2 --CO--NH--R.sub.4 group wherein R.sub.4 is a substituted or unsubstituted alkyl, arly or aralkyl or ##STR3## radical and R represents the branched chain on an aminoacid. PA1 the reaction of a dextran with a derivative of the formula: EQU X(CH.sub.2).sub.n --R--COOH PA1 in which X represents a reactive group capable of establishing a glucosylation link with a --OH group of glucosyl unit, which results in the formation of B units, PA1 The reaction of the dextran containing the A and B units with a derivative of formula ##STR12## in which R.sub.1 is as defined above in order to obtain the fixation through an amide bridge of the substituted aryl group with the radical coming from the substituent chains of the B units, which permits the introduction of C units onto the chain, PA1 introduction of anions such as SO.sub.3.sup.- on the aryl groups of the C units to obtain the D units, PA1 fractionation, optionally of the dextran derivatives, in order to eliminate the derivatives having a molecular weight less than 5000.
The researches of the Applicants in this field has brought them to study a polysaccharide already known, namely dextran.
Dextran is a polyglucoside of molecular weight from about 5000 to several millions of daltons, formed by glucosyl units A with linkages essentially of the 1-6 type of the formula: ##STR4##
In the therapeutical uses, dextrans having molecular weights less than about 100,000 are generally used.
Dextran is used particularly, as a blood plasma substitute or at least as an expander. These uses can result however, in certain cases, in immunitary shocks.
The studies carried out have shown that the simultaneous presence of certain substituent groups, in predetermined proportions, on dextran chains free of aminoacids, confered to the dextrans biological properties of great interest and high tolerance.
Accordingly it is an object of the invention to provide derivatives of dextran having at least certain of the biological properties of heparin and useful as bio-materials due to their high tolerance.
It is also an object of the invention to provide a process for the preparation of these derivatives which is easy to put into practice.
It is equally an object to provide soluble biomaterials and medicaments or vectors of medicaments of high efficiency based on these derivatives having the advantage of being obtained synthetically.